Base de dados : MEDLINE
Pesquisa : D09.408.620.569.070.125.600 [Categoria DeCS]
Referências encontradas : 1415 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 142 ir para página                         

  1 / 1415 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29220653
[Au] Autor:Singh HR; Nardozza AP; Möller IR; Knobloch G; Kistemaker HAV; Hassler M; Harrer N; Blessing C; Eustermann S; Kotthoff C; Huet S; Mueller-Planitz F; Filippov DV; Timinszky G; Rand KD; Ladurner AG
[Ad] Endereço:Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Street 9, 82152 Planegg-Martinsried, Germany.
[Ti] Título:A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene.
[So] Source:Mol Cell;68(5):860-871.e7, 2017 Dec 07.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase. ALC1 fragments lacking the regulatory macrodomain relax chromatin in vivo without requiring PARP1 activation. Further, the ATPase restricts the macrodomain's interaction with PARP1 under non-DNA damage conditions. Somatic cancer mutants disrupt ALC1's auto-inhibition and activate chromatin remodeling. Our data show that the NAD -metabolite and nucleic acid PAR triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation.
[Mh] Termos MeSH primário: Montagem e Desmontagem da Cromatina
Dano ao DNA
DNA Helicases/metabolismo
Proteínas de Ligação a DNA/metabolismo
Neoplasias/enzimologia
Poli(ADP-Ribose) Polimerase-1/metabolismo
Poli Adenosina Difosfato Ribose/metabolismo
[Mh] Termos MeSH secundário: Regulação Alostérica
Sítios de Ligação
Linhagem Celular Tumoral
DNA Helicases/química
DNA Helicases/genética
Proteínas de Ligação a DNA/química
Proteínas de Ligação a DNA/genética
Ativação Enzimática
Seres Humanos
Mutação
Neoplasias/genética
Neoplasias/patologia
Conformação de Ácido Nucleico
Poli(ADP-Ribose) Polimerase-1/química
Poli(ADP-Ribose) Polimerase-1/genética
Poli ADP Ribosilação
Poli Adenosina Difosfato Ribose/química
Ligação Proteica
Relação Estrutura-Atividade
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 26656-46-2 (Poly Adenosine Diphosphate Ribose); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1); EC 3.6.4.- (DNA Helicases); EC 3.6.4.12 (CHD1L protein, human)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


  2 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28854736
[Au] Autor:Liu C; Vyas A; Kassab MA; Singh AK; Yu X
[Ad] Endereço:Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
[Ti] Título:The role of poly ADP-ribosylation in the first wave of DNA damage response.
[So] Source:Nucleic Acids Res;45(14):8129-8141, 2017 Aug 21.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Poly ADP-ribose polymerases (PARPs) catalyze massive protein poly ADP-ribosylation (PARylation) within seconds after the induction of DNA single- or double-strand breaks. PARylation occurs at or near the sites of DNA damage and promotes the recruitment of DNA repair factors via their poly ADP-ribose (PAR) binding domains. Several novel PAR-binding domains have been recently identified. Here, we summarize these and other recent findings suggesting that PARylation may be the critical event that mediates the first wave of the DNA damage response. We also discuss the potential for functional crosstalk with other DNA damage-induced post-translational modifications.
[Mh] Termos MeSH primário: Dano ao DNA
Reparo do DNA
DNA/genética
Poli Adenosina Difosfato Ribose/metabolismo
[Mh] Termos MeSH secundário: Sítios de Ligação/genética
DNA/metabolismo
Quebras de DNA de Cadeia Dupla
Quebras de DNA de Cadeia Simples
Seres Humanos
Modelos Biológicos
Fosforilação
Poli(ADP-Ribose) Polimerases/metabolismo
Ligação Proteica
Processamento de Proteína Pós-Traducional
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
26656-46-2 (Poly Adenosine Diphosphate Ribose); 9007-49-2 (DNA); EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx565


  3 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28523544
[Au] Autor:Kim HD; Call T; Magazu S; Ferguson D
[Ad] Endereço:Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, 85004, USA.
[Ti] Título:Drug Addiction and Histone Code Alterations.
[So] Source:Adv Exp Med Biol;978:127-143, 2017.
[Is] ISSN:0065-2598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acute and prolonged exposure to drugs of abuse induces changes in gene expression, synaptic function, and neural plasticity in brain regions involved in reward. Numerous genes are involved in this process, and persistent changes in gene expression coincide with epigenetic histone modifications and DNA methylation. Histone modifications are attractive regulatory mechanisms, which can encode complex environmental signals in the genome of postmitotic cells, like neurons. Recently, it has been demonstrated that specific histone modifications are involved in addiction-related gene regulatory mechanisms, by a diverse set of histone-modifying enzymes and readers. These histone modifiers and readers may prove to be valuable pharmacological targets for effective treatments for drug addiction.
[Mh] Termos MeSH primário: Epigênese Genética/genética
Código das Histonas/efeitos dos fármacos
Drogas Ilícitas/farmacologia
Transtornos Relacionados ao Uso de Substâncias/genética
[Mh] Termos MeSH secundário: Acetilação
Encéfalo/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Código das Histonas/genética
Código das Histonas/fisiologia
Seres Humanos
Metilação
Proteínas do Tecido Nervoso/metabolismo
Fosforilação
Poli Adenosina Difosfato Ribose/metabolismo
Processamento de Proteína Pós-Traducional/efeitos dos fármacos
Recompensa
Drogas Ilícitas/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Nerve Tissue Proteins); 0 (Street Drugs); 26656-46-2 (Poly Adenosine Diphosphate Ribose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE
[do] DOI:10.1007/978-3-319-53889-1_7


  4 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28383827
[Au] Autor:Palazzo L; Mikoc A; Ahel I
[Ad] Endereço:Sir William Dunn School of Pathology, University of Oxford, UK.
[Ti] Título:ADP-ribosylation: new facets of an ancient modification.
[So] Source:FEBS J;284(18):2932-2946, 2017 Sep.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Rapid response to environmental changes is achieved by uni- and multicellular organisms through a series of molecular events, often involving modification of macromolecules, including proteins, nucleic acids and lipids. Amongst these, ADP-ribosylation is of emerging interest because of its ability to modify different macromolecules in the cells, and its association with many key biological processes, such as DNA-damage repair, DNA replication, transcription, cell division, signal transduction, stress and infection responses, microbial pathogenicity and aging. In this review, we provide an update on novel pathways and mechanisms regulated by ADP-ribosylation in organisms coming from all kingdoms of life.
[Mh] Termos MeSH primário: ADP Ribose Transferases/genética
Envelhecimento/metabolismo
Reparo do DNA
Poli Adenosina Difosfato Ribose/metabolismo
Processamento de Proteína Pós-Traducional
[Mh] Termos MeSH secundário: ADP Ribose Transferases/metabolismo
Envelhecimento/genética
Animais
Archaea/genética
Archaea/metabolismo
Bactérias/genética
Bactérias/metabolismo
Evolução Biológica
Dano ao DNA
Replicação do DNA
Expressão Gênica
Seres Humanos
Isoenzimas/genética
Isoenzimas/metabolismo
Diester Fosfórico Hidrolases/genética
Diester Fosfórico Hidrolases/metabolismo
Pirofosfatases/genética
Pirofosfatases/metabolismo
Transdução de Sinais
Vírus/genética
Vírus/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Isoenzymes); 26656-46-2 (Poly Adenosine Diphosphate Ribose); EC 2.4.2.- (ADP Ribose Transferases); EC 3.1.4.- (Phosphoric Diester Hydrolases); EC 3.1.4.1 (ectonucleotide pyrophosphatase phosphodiesterase 1); EC 3.6.1.- (Pyrophosphatases); EC 3.6.1.- (nudix hydrolases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14078


  5 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28130107
[Au] Autor:Nakajima H; Itakura M; Sato K; Nakamura S; Azuma YT; Takeuchi T
[Ad] Endereço:Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-kita, Izumisano, Osaka, 5988531, Japan. Electronic address: hnakajima@vet.osakafu-u.ac.jp.
[Ti] Título:Extracellular poly(ADP-ribose) is a neurotrophic signal that upregulates glial cell line-derived neurotrophic factor (GDNF) levels in vitro and in vivo.
[So] Source:Biochem Biophys Res Commun;484(2):385-389, 2017 Mar 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Synthesis of poly(ADP-ribose) (PAR) is catalyzed by PAR polymerase-1 (PARP-1) in neurons. PARP1 plays a role in various types of brain damage in neurodegenerative disorders. In neurons, overactivation of PARP-1 during oxidative stress induces robust PAR formation, which depletes nicotinamide adenine dinucleotide levels and leads to cell death. However, the role of the newly-formed PAR in neurodegenerative disorders remains elusive. We hypothesized that the effects of PAR could occur in the extracellular space after it is leaked from damaged neurons. Here we report that extracellular PAR (EC-PAR) functions as a neuroprotective molecule by inducing the synthesis of glial cell line-derived neurotrophic factor (GDNF) in astrocytes during neuronal cell death, both in vitro and in vivo. In primary rat astrocytes, exogenous treatment with EC-PAR produced GDNF but not other neurotrophic factors. The effect was concentration-dependent and did not affect cell viability in rat C6 astrocytoma cells. Topical injection of EC-PAR into rat striatum upregulated GDNF levels in activated astrocytes and improved pathogenic rotation behavior in a unilateral 6-hydroxydopamine model of Parkinson disease in rats. These findings indicate that EC-PAR acts as a neurotrophic enhancer by upregulating GDNF levels. This effect protects the remaining neurons following oxidative stress-induced brain damage, such as that seen with Parkinson disease.
[Mh] Termos MeSH primário: Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo
Poli Adenosina Difosfato Ribose/metabolismo
[Mh] Termos MeSH secundário: Animais
Astrócitos/metabolismo
Linhagem Celular Tumoral
Células Cultivadas
Modelos Animais de Doenças
Espaço Extracelular/metabolismo
Técnicas In Vitro
Fatores de Crescimento Neural/metabolismo
Doença de Parkinson/terapia
Ratos
Ratos Wistar
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glial Cell Line-Derived Neurotrophic Factor); 0 (Nerve Growth Factors); 26656-46-2 (Poly Adenosine Diphosphate Ribose)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170627
[Lr] Data última revisão:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170129
[St] Status:MEDLINE


  6 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28107648
[Au] Autor:Luo X; Ryu KW; Kim DS; Nandu T; Medina CJ; Gupte R; Gibson BA; Soccio RE; Yu Y; Gupta RK; Kraus WL
[Ad] Endereço:Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center,
[Ti] Título:PARP-1 Controls the Adipogenic Transcriptional Program by PARylating C/EBPß and Modulating Its Transcriptional Activity.
[So] Source:Mol Cell;65(2):260-271, 2017 Jan 19.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPß, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPß's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models. Interestingly, PARP-1 catalytic activity drops precipitously during the first 48 hr of differentiation, corresponding to a release of C/EBPß from PARylation-mediated inhibition. This promotes the binding of C/EBPß at enhancers controlling the expression of adipogenic target genes and continued differentiation. Depletion or chemical inhibition of PARP-1, or mutation of the PARylation sites on C/EBPß, enhances these early adipogenic events. Collectively, our results provide a clear example of how site-specific PARylation drives biological outcomes.
[Mh] Termos MeSH primário: Adipócitos/enzimologia
Adipogenia
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo
Células-Tronco Embrionárias/enzimologia
Poli(ADP-Ribose) Polimerase-1/metabolismo
Poli Adenosina Difosfato Ribose/metabolismo
Processamento de Proteína Pós-Traducional
Transcrição Genética
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/efeitos dos fármacos
Adipogenia/efeitos dos fármacos
Animais
Sítios de Ligação
Proteína beta Intensificadora de Ligação a CCAAT/genética
DNA/genética
DNA/metabolismo
Células-Tronco Embrionárias/efeitos dos fármacos
Genótipo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Mutação
Células NIH 3T3
Fenótipo
Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores
Poli(ADP-Ribose) Polimerase-1/deficiência
Poli(ADP-Ribose) Polimerase-1/genética
Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia
Ligação Proteica
Domínios Proteicos
Interferência de RNA
Transdução de Sinais
Fatores de Tempo
Transcrição Genética/efeitos dos fármacos
Ativação Transcricional
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCAAT-Enhancer-Binding Protein-beta); 0 (Cebpb protein, mouse); 0 (Poly(ADP-ribose) Polymerase Inhibitors); 26656-46-2 (Poly Adenosine Diphosphate Ribose); 9007-49-2 (DNA); EC 2.4.2.30 (Parp1 protein, mouse); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE


  7 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28099491
[Au] Autor:Ponath V; Kaina B
[Ad] Endereço:Department of Toxicology, University Medical Center, Mainz, Germany.
[Ti] Título:Death of Monocytes through Oxidative Burst of Macrophages and Neutrophils: Killing in Trans.
[So] Source:PLoS One;12(1):e0170347, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Monocytes and their descendants, macrophages, play a key role in the defence against pathogens. They also contribute to the pathogenesis of inflammatory diseases. Therefore, a mechanism maintaining a balance in the monocyte/macrophage population must be postulated. Our previous studies have shown that monocytes are impaired in DNA repair, rendering them vulnerable to genotoxic stress while monocyte-derived macrophages are DNA repair competent and genotoxic stress-resistant. Based on these findings, we hypothesized that monocytes can be selectively killed by reactive oxygen species (ROS) produced by activated macrophages. We also wished to know whether monocytes and macrophages are protected against their own ROS produced following activation. To this end, we studied the effect of the ROS burst on DNA integrity, cell death and differentiation potential of monocytes. We show that monocytes, but not macrophages, stimulated for ROS production by phorbol-12-myristate-13-acetate (PMA) undergo apoptosis, despite similar levels of initial DNA damage. Following co-cultivation with ROS producing macrophages, monocytes displayed oxidative DNA damage, accumulating DNA single-strand breaks and a high incidence of apoptosis, reducing their ability to give rise to new macrophages. Killing of monocytes by activated macrophages, termed killing in trans, was abolished by ROS scavenging and was also observed in monocytes co-cultivated with ROS producing activated granulocytes. The data revealed that monocytes, which are impaired in the repair of oxidised DNA lesions, are vulnerable to their own ROS and ROS produced by macrophages and granulocytes and support the hypothesis that this is a mechanism regulating the amount of monocytes and macrophages in a ROS-enriched inflammatory environment.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Quebras de DNA de Cadeia Simples/efeitos dos fármacos
Reparo do DNA/genética
Macrófagos/metabolismo
Monócitos/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Explosão Respiratória/fisiologia
[Mh] Termos MeSH secundário: Sobrevivência Celular/fisiologia
Células Cultivadas
Proteínas de Ligação a DNA/metabolismo
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo
Granulócitos/metabolismo
Seres Humanos
Ativação de Macrófagos/genética
Neutrófilos/metabolismo
Ésteres de Forbol/farmacologia
Poli(ADP-Ribose) Polimerase-1/metabolismo
Poli Adenosina Difosfato Ribose/metabolismo
Linfócitos T/metabolismo
Proteína 1 Complementadora Cruzada de Reparo de Raio-X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA-Binding Proteins); 0 (Phorbol Esters); 0 (Reactive Oxygen Species); 0 (X-ray Repair Cross Complementing Protein 1); 20839-06-9 (phorbol-12-myristate); 26656-46-2 (Poly Adenosine Diphosphate Ribose); 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170347


  8 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27979751
[Au] Autor:Huang K; Du M; Tan X; Yang L; Li X; Jiang Y; Wang C; Zhang F; Zhu F; Cheng M; Yang Q; Yu L; Wang L; Huang D; Huang K
[Ad] Endereço:Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
[Ti] Título:PARP1-mediated PPARα poly(ADP-ribosyl)ation suppresses fatty acid oxidation in non-alcoholic fatty liver disease.
[So] Source:J Hepatol;66(5):962-977, 2017 05.
[Is] ISSN:1600-0641
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND & AIMS: PARP1 is a key mediator of cellular stress responses and critical in multiple physiological and pathophysiological processes of cells. However, whether it is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) remains elusive. METHODS: We analysed PARP1 activity in the liver of mice on a high fat diet (HFD), and samples from NAFLD patients. Gain- or loss-of-function approaches were used to investigate the roles and mechanisms of hepatic PARP1 in the pathogenesis of NAFLD. RESULTS: PARP1 is activated in fatty liver of HFD-fed mice. Pharmacological or genetic manipulations of PARP1 are sufficient to alter the HFD-induced hepatic steatosis and inflammation. Mechanistically we identified peroxisome proliferator-activated receptor α (PPARα) as a substrate of PARP1-mediated poly(ADP-ribosyl)ation. This poly(ADP-ribosyl)ation of PPARα inhibits its recruitment to target gene promoters and its interaction with SIRT1, a key regulator of PPARα signaling, resulting in suppression of fatty acid oxidation upregulation induced by fatty acids. Moreover, we show that PARP1 is a transcriptional repressor of PPARα gene in human hepatocytes, and its activation suppresses the ligand (fenofibrate)-induced PPARα transactivation and target gene expression. Importantly we demonstrate that liver biopsies of NAFLD patients display robust increases in PARP activity and PPARα poly(ADP-ribosyl)ation levels. CONCLUSIONS: Our data indicate that PARP1 is activated in fatty liver, which prevents maximal activation of fatty acid oxidation by suppressing PPARα signaling. Pharmacological inhibition of PARP1 may alleviate PPARα suppression and therefore have therapeutic potential for NAFLD. LAY SUMMARY: PARP1 is activated in the non-alcoholic fatty liver of mice and patients. Inhibition of PARP1 activation alleviates lipid accumulation and inflammation in fatty liver of mice.
[Mh] Termos MeSH primário: Ácidos Graxos/metabolismo
Hepatopatia Gordurosa não Alcoólica/metabolismo
PPAR alfa/metabolismo
Poli(ADP-Ribose) Polimerase-1/fisiologia
Poli Adenosina Difosfato Ribose/metabolismo
[Mh] Termos MeSH secundário: Animais
Dieta Hiperlipídica
Células Hep G2
Hepatócitos/metabolismo
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Oxirredução
Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/fisiologia
Sirtuína 1/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fatty Acids); 0 (PPAR alpha); 0 (PPARGC1A protein, human); 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha); 26656-46-2 (Poly Adenosine Diphosphate Ribose); EC 2.4.2.30 (PARP1 protein, human); EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1); EC 3.5.1.- (SIRT1 protein, human); EC 3.5.1.- (Sirtuin 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161217
[St] Status:MEDLINE


  9 / 1415 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27518087
[Au] Autor:Long A; Park JH; Klimova N; Fowler C; Loane DJ; Kristian T
[Ad] Endereço:Veterans Affairs Maryland Health Care System, 10 North Greene Street, Baltimore, MD, 21201, USA.
[Ti] Título:CD38 Knockout Mice Show Significant Protection Against Ischemic Brain Damage Despite High Level Poly-ADP-Ribosylation.
[So] Source:Neurochem Res;42(1):283-293, 2017 Jan.
[Is] ISSN:1573-6903
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Several enzymes in cellular bioenergetics metabolism require NAD as an essential cofactor for their activity. NAD depletion following ischemic insult can result in cell death and has been associated with over-activation of poly-ADP-ribose polymerase PARP1 as well as an increase in NAD consuming enzyme CD38. CD38 is an NAD glycohydrolase that plays an important role in inflammatory responses. To determine the contribution of CD38 activity to the mechanisms of post-ischemic brain damage we subjected CD38 knockout (CD38KO) mice and wild-type (WT) mice to transient forebrain ischemia. The CD38KO mice showed a significant amelioration in both histological and neurologic outcome following ischemic insult. Decrease of hippocampal NAD levels detected during reperfusion in WT mice was only transient in CD38KO animals, suggesting that CD38 contributes to post-ischemic NAD catabolism. Surprisingly, pre-ischemic poly-ADP-ribose (PAR) levels were dramatically higher in CD38KO animals compared to WT animals and exhibited reduction post-ischemia in contrast to the increased levels in WT animals. The high PAR levels in CD38 mice were due to reduced expression levels of poly-ADP-ribose glycohydrolase (PARG). Thus, the absence of CD38 activity can not only directly affect inflammatory response, but also result in unpredicted alterations in the expression levels of enzymes participating in NAD metabolism. Although the CD38KO mice showed significant protection against ischemic brain injury, the changes in enzyme activity related to NAD metabolism makes the determination of the role of CD38 in mechanisms of ischemic brain damage more complex.
[Mh] Termos MeSH primário: ADP-Ribosil Ciclase 1/metabolismo
Isquemia Encefálica/metabolismo
Isquemia Encefálica/prevenção & controle
Glicoproteínas de Membrana/metabolismo
Poli Adenosina Difosfato Ribose/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Glicosídeo Hidrolases/metabolismo
Hipocampo/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Distribuição Aleatória
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Glycoproteins); 26656-46-2 (Poly Adenosine Diphosphate Ribose); EC 3.2.1.- (Glycoside Hydrolases); EC 3.2.1.143 (poly ADP-ribose glycohydrolase); EC 3.2.2.5 (Cd38 protein, mouse); EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160813
[St] Status:MEDLINE
[do] DOI:10.1007/s11064-016-2031-9


  10 / 1415 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
[PMID]:27817744
[Au] Autor:Miwa M; Ida C; Yamashita S; Tanaka M; Fujisawa J
[Ad] Endereço:Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan. m_miwa@nagahama-i-bio.ac.jp.
[Ti] Título:Poly(ADP-ribose): Structure, Physicochemical Properties and Quantification In Vivo, with Special Reference to Poly(ADP-ribose) Binding Protein Modules.
[So] Source:Curr Protein Pept Sci;17(7):683-692, 2016.
[Is] ISSN:1875-5550
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:PolyADP-ribosylation is a unique posttranslational modification of proteins, involved in various cellular functions including stability of chromatin. PolyADP-ribosylation modifies acceptor proteins with a large negatively charged poly(ADP-ribose) (PAR) to greatly change the structure and function of the acceptor proteins. In addition various specific motifs of proteins were recently found to interact non-covalently with PAR thereby changing the spaciotemporal activity of protein-protein interaction in cells. However, the structure of PAR to which specific protein motifs should bind is not fully characterized. The present work will review the structure, physicochemical properties and quantification of PAR in vivo, with special reference to PAR binding protein modules.
[Mh] Termos MeSH primário: Proteínas de Transporte/química
Proteínas de Transporte/metabolismo
Poli Adenosina Difosfato Ribose/química
Poli Adenosina Difosfato Ribose/metabolismo
Poli(ADP-Ribose) Polimerases/química
Poli(ADP-Ribose) Polimerases/metabolismo
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Proteínas de Transporte/genética
Glicosilação
Seres Humanos
Mutação
Poli(ADP-Ribose) Polimerases/genética
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Carrier Proteins); 26656-46-2 (Poly Adenosine Diphosphate Ribose); EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170209
[Lr] Data última revisão:
170209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161108
[St] Status:MEDLINE



página 1 de 142 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde